ABSTRACT. Benzo[a]pyrene (BP), one of many polycyclic aromatic hydrocarbon environmental pollutants, is metabolized to an array of regio- and stereoisomeric BP diol epoxides (BPDE), including the highly potent carcinogen (+)- anti-BPDE. Each metabolite stereoisomer can be nucleophilicity coupled at the benzylic site to the exocyclic amino groups of nucleobases. In addition to enzymatic and hydroytic removal of BPDE lesions from DNA, it has been reported that oligomeric and monomeric adducts undergo chemical decomposition, through the mechanism and byproducts of this process are unknown. We propose to investigate the hypotheses that BPDE-modified DNA degrades via a homolytic process that is conformationally promoted by nucleobase-pyrene stacking. To test this hypothesis we will examine the conformations and degradations of a series of monomer BPDE-deoxynucleotide adducts that vary in nucleobase and BP stereochemistry. Specifically, we will examine these species for evidence that intralesion charge transfer interaction precede degradation, and third, we will investigate the occurrence of these processes in BPDE-modified single-stranded and duplex DNA. In preliminary studies, we investigated the decompositions of model compounds that support a pyrene and aryl unit tethered by a C-N linkage similar to that of BPDE-deoxynucleotide adducts. These studies suggested that adducts degrade at different that are correlated with conformational properties. Further investigations will examine the aryl size, aryl electronics, solvent and degradation byproducts to provide insight on the degradations on BPDE-deoxynucleotide adduct. These studies contribute to the understand of BPO carcinogenesis in two important areas. First, a major thrust of this proposal is to survey the conformational properties of monomer BPDE-deoxynucleotide adducts. These studies contribute to the understanding of BP carcinogenesis in two important areas. First, a major thrust of this proposal is to survey the conformational properties of monomer BPDE-Deoxynucleotide adducts as a function of nucleobase and stereochemistry. These units may be important contributors to the conformational properties of adducted DNA and thus may be consequential in the erroneous bioprocessing at lesions. Second, BPDE-DNA adduct degradation via homo or heterolytic pathways may induce DNA damage at flanking residues that may contribute to the tumorigenic process.